关键词： B4GALNT1   ganglioside   glycosphingolipid   hereditary spastic paraplegia   golgi   termination codon  

摘要： B4GALNT1 is an enzyme essential for the synthesis of complex gangliosides, whose absence leads to progressive neurodegeneration with aging in mice. Recently, eleven cases of hereditary spastic paraplegia with mutation in the coding region of B4GALNT1 were reported. However, changes in the enzymatic activity of their products have never been studied. We have constructed expression vectors for individual mutant cDNAs, and examined their activities by cell free in vitro enzyme assays, and flow cytometry of cells transfected with their expression vectors. Among them, almost all mutant genes showed the complete loss of B4GALNT1 activity in both the in vitro enzyme assays and flow cytometry. Two mutants exceptionally showed weak activity. One of them, M4, had a mutation at amino acid 228 with a premature termination codon. Interestingly, the intensity of fluorescence of GM2 measured by flow cytometry was equivalent between the WT and M4 mutant, although the positive cell population was relatively small in M4. Western immunoblotting of cell lysates from transfectants with cDNA plasmids revealed 67-kDa bands except those containing premature termination codons or frame-shift mutation. Taken together with the clinical findings of patients, loss of enzyme activity may be responsible for the clinical features of hereditary spastic paraplegia, whereas the intensity of neurological disorders was relatively milder than expected. These clinical features of patients including those with male hypogonadism are very similar to the abnormal phenotypes detected in B4galnt1-deficient mice. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

关键词： SOX2   Antibodies   Paraneoplastic   Lambert-Eaton myasthenic syndrome   Small-cell lung cancer  

摘要： Antibodies to SOXB1 proteins in patients with paraneoplastic disorders are associated with small-cell lung cancer (SCLC), particularly in Lambert-Eaton myasthenic syndrome (LEMS). We aimed to establish if SOX2 antibodies could be used to identify SCLC and other tumours found in a range of paraneoplastic disorders and controls. SOX2 antibodies were detectable in 61% of patients with LEMS-SCLC, and in other paraneoplastic disorders, such as opsoclonus-myoclonus and paraneoplastic cerebellar degeneration, only when there was an underlying SCLC. SOX2 antibodies are specific (> 90%) markers for SCLC, but are rarely found in patients with other tumours, whether neurological symptoms are present or not.

关键词： Acute ischemic stroke   Heart rate variability   Fractal dimension   Recurrent ischemic stroke   Early neurological deterioration  

摘要： Acute ischemic stroke (AIS) may experience early neurological deterioration (END) and have high risks of recurrent ischemic strokes (RIS), which are often associated with a poor outcome. Post-stroke prognosis is associated with autonomic status. Recently, studies showed that heart rate variability (HRV) is an early outcome predictor in acute stroke patients. The purpose of our study was to investigate association decreased HRV by fractal dimension (FD) with early END within 72 h of admission and 1-year RIS. In this study, we assessed autonomic function of ischemic stroke patients within 24 h from symptom onset by FD. Receiver operating characteristic (ROC) curve was utilized to determine the optimal cut point of FD for END and RIS. 516 patients (mean age 66.14 +/- 10.11) with acute ischemic stroke underwent a comprehensive clinical investigation and FD test. According to the data of FD, we investigated association with END within 72 h of admission and the 1-year RIS. ROC curve analysis shown that the optimal cut point of FD for END and RIS were FD <= 1.05 and FD <= 1.15 respectively. In fully adjusted models, there was an association between FD 5 1.05 and END (adjusted odds ratio, 2.64;95% confidence interval, 1.55-4.49;P < 0.001), there was an association between FD < 1.15 and RIS (adjusted odds ratio,5.40;95% confidence interval, 3.02-9.64;P < .001). These findings indicate that FD <= 1.05 and FD <= 1.15 were independently associated with increased risk of END and RIS respectively, which may have predictive value in END and RIS.

关键词： Neuroimmunology   Regulatory T cells  

摘要： In addition to maintaining immune tolerance, FOXP3(+) regulatory T (T-reg) cells perform specialized functions in tissue homeostasis and remodelling(1,2). However, the characteristics and functions of brain Treg cells are not well understood because there is a low number of Treg cells in the brain under normal conditions. Here we show that there is massive accumulation of T-reg cells in the mouse brain after ischaemic stroke, and this potentiates neurological recovery during the chronic phase of ischaemic brain injury. Although brain T-reg cells are similar to Treg cells in other tissues such as visceral adipose tissue and muscle(3-5), they are apparently distinct and express unique genes related to the nervous system including Htr7, which encodes the serotonin receptor 5-HT7. The amplification of brain T-reg cells is dependent on interleukin (IL)-2, IL-33, serotonin and T cell receptor recognition, and infiltration into the brain is driven by the chemokines CCL1 and CCL20. Brain T-reg cells suppress neurotoxic astrogliosis by producing amphiregulin, a low-affinity epidermal growth factor receptor (EGFR) ligand. Stroke is a leading cause of neurological disability, and there are currently few effective recovery methods other than rehabilitation during the chronic phase. Our findings suggest that T-reg cells and their products may provide therapeutic opportunities for neuronal protection against stroke and neuroinflammatory diseases.

关键词： Cysteinyl leukotrienes   Alzheimer's disease   5-lipoxygenase   Montelukast   Pranlukast   HAMI 3379  

摘要： Cysteinyl leukotrienes (cysLTs) are member of eicosanoid inflammatory lipid mediators family produced by oxidation of arachidonic acid by action of the enzyme 5-lipoxygenase (5-LOX). 5-LOX is activated by enzyme 5-Lipoxygenase-activating protein (FLAP), which further lead to production of cysLTs i.e. leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4). CysLTs then produce their potent inflammatory actions by activating CysLT1 and CysLT2 receptors. Inhibitors of cysLTs are indicated in asthma, allergic rhinitis and other inflammatory disorders. Earlier studies have associated cysLTs and their receptors in several neurodegenerative disorders diseases like, multiple sclerosis, Parkinson's disease, Huntington's disease, epilepsy and Alzheimer's disease (AD). These inflammatory lipid mediators have previously shown effects on various aggravating factors of AD. However, not much data has been elucidated to test their role against AD clinically. Herein, through this review, we have provided the current and emerging information on the role of cysLTs and their receptors in various neurological complications responsible for the development of AD. In addition, literature evidences for the effect of cysLT inhibitors on distinct aspects of abnormalities in AD has also been reviewed. Promising advancement in understanding on the role of cysLTs on the various neuromodulatory processes and mechanisms may contribute to the development of newer and safer therapy for the treatment of AD in future.

关键词： Preterm   neurological assessment   executive functions   behavior   quality of life  

摘要： Objective: This prospective study investigated the relationship between Amiel-Tison neurological assessment (ATNA) in preterm children and their psychosocial functioning in adolescence. Methods: From the initial group of 45 children regularly assessed by the ATNA from term until the age of 2 years, 27 participated in the follow-up at 13 years. Results: Of the three groups categorized by neurological signs as normal, intermediate or abnormal, parents of adolescents with normal ATNA reported the lowest number of executive function problems (p = 0.019) and behavioral symptoms (p = 0.011), while the adolescents themselves reported the lowest number of behavioral symptoms (p = 0.005) and the highest quality of life (p = 0.012). The number of problems reported increased with the number of abnormal neurological signs. Conclusion: Standardized neurological assessment may be a helpful clinical tool for the identification of children at risk for later psychosocial problems who could benefit from prevention and early intervention programs.

关键词： Pineal cyst   intracranial hypertension   CSF flow obstruction  

摘要： Purpose: Management of patients presenting for various nonspecific complaints without clear neurological abnormalities and with normal ventricular size remains highly controversial. We intended to share our rationale for surgical treatment of patients who show symptoms of transient increase of intracranial pressure owing to the presence of the cyst. Materials and methods: We have retrospectively analyzed 28 cases of patients who presented without Parinaud syndrome nor ventricular enlargement and underwent pineal cyst removal in our centre between 2007 and 2015. We analyzed patients' age, sex, symptoms, preoperative cyst size, perioperative course, treatment outcome and neurologic status at discharge and at follow-up visits 4 and 12 months afterwards. Results: Main complaints included paroxysmal headaches, nausea, vomiting, visual disturbances, syncope and transient depression of consciousness. Mean age of patients was 31 years (17-55);there were 24 females and 4 males. Mean cyst diameter was 17 mm (10-26). Decision about surgical treament was based on signs of transient increases of intracranial pressure. All patients underwent complete cyst excision via midline suboccipital craniotomy and infratentorial supracerebellar route. Short-lasting perioperative neurological signs (notably upgaze palsy) were noted in 22 cases and uniformly resolved within the observation period of 12 months. Conclusion: Abnormal neurological findings and ventricular enlargement are not indispensable to justify surgical treatment of pineal cysts. Judicious selection of surgical candidates based predominantly on clinical grounds can lead to excellent operative results.

关键词： Whole exome sequencing   consanguinity   APOPT1   KCNJ10   MEM70   MFN2   NSUN2   OPA1   PNKP  

摘要： There is increasing evidence that whole exome sequencing (WES) has a high diagnostic yield and is cost-efficient for individuals with neurological phenotypes. However, there is limited data on the use of WES in non-Western populations, including populations with a high rate of consanguinity. Retrospective chart review was performed on 24 adults with undiagnosed neurological symptoms evaluated in genetics and neurology clinics in a tertiary care facility on the Arabian Peninsula, and had WES between 2014 and 2016. Definitive diagnoses were made in 13/24 (54%) of cases. Of these, 5/13 (38%) revealed novel pathogenic variants. Of the known 19/24 (79%) consanguineous cases, diagnostic rate was slightly higher, 11/19 (58%) as compared to 2/5 (40%) among non-consanguineous cases. Autosomal recessive disorders comprised 10/13 (77%) of molecular diagnoses, all found to be due to homozygous pathogenic variants among consanguineous cases. WES in this cohort of adults with neurological symptoms had a high diagnostic rate likely due to high consanguinity rates in this population, as evidenced by the high diagnostic rate of homozygous pathogenic variants.

关键词： exosomes   extracellular vesicles   nervous system   central nervous system   cell-cell interaction   biomarkers   theranostics tools   neurological diseases  

摘要： Extracellular vesicles (EVs), including exosomes, are membranous particles released by cells into the extracellular space. They are involved in cell differentiation, tissue homeostasis, and organ remodelling in virtually all tissues, including the central nervous system (CNS). They are secreted by a range of cell types and via blood reaching other cells whose functioning they can modify because they transport and deliver active molecules, such as proteins of various types and functions, lipids, DNA, and miRNAs. Since they are relatively easy to isolate, exosomes can be characterized, and their composition elucidated and manipulated by bioengineering techniques. Consequently, exosomes appear as promising theranostics elements, applicable to accurately diagnosing pathological conditions, and assessing prognosis and response to treatment in a variety of disorders. Likewise, the characteristics and manageability of exosomes make them potential candidates for delivering selected molecules, e.g., therapeutic drugs, to specific target tissues. All these possible applications are pertinent to research in neurophysiology, as well as to the study of neurological disorders, including CNS tumors, and autoimmune and neurodegenerative diseases. In this brief review, we discuss what is known about the role and potential future applications of exosomes in the nervous system and its diseases, focusing on cell-cell communication in physiology and pathology.

关键词： Bandages   child   kinesiology   Sialorrhea   speech therapy  

摘要： Objective: To evaluate the effects of Kinesio Taping (KT) of the orbicularis oris muscles as an adjunct to standard therapy for drooling. Methods: Fifteen children with neurological disorders and drooling received speech therapy and twice-weekly KT of the orbicularis muscles over a 30-day period. Drooling was assessed by six parameters: impact on the life of the child and caregiver;severity of drooling;frequency of drooling;drooling volume (estimated by number of bibs used);salivary leak;and interlabial gap. Seven markers of oral motor skills were also assessed. Results: KT of the orbicularis oris region reduced the interlabial gap. All oral motor skills and almost all markers of drooling improved after 15 days of treatment. Conclusion: In this sample of children with neurological disorders, adding KT of the orbicularis oris muscles to speech therapy caused rapid improvement in oral motor skills and drooling.